Sulphoxides formation

An important industrial process using peracetic acid for sulphoxide formation is that of 7-ADCA (7-aminodeacetoxycephalosporanic acid, a cephalosporin antibiotic precursor) production, in which penicillin is oxidised to sulphoxide followed by ring-expansion [218] (Figure 9.11). 

Sulphoxide formation. A small amount of sulphoxide formation is not uncommon... 

Aksnes A. Methionine sulphoxide formation, occurrence and biological availability. A review. Fiskeridirektoratets Skrifter, Serie Erncering, 2 (5) 125-153 (1984). 

Sulphinic acids. Aromatic sulphinic acids are found in Solubility Group II. They may be detected by dissolving in cold concentrated sulphuric acid and adding one drop of phenetole or anisole when a blue colour is produced (Smiles s test), due to the formation of a para-substituted aromatic sulphoxide. Thus the reaction with benzenesulphinic acid is ... 

In addition to nitration, oxidation of the S atom also takes place, resulting in the formation of the sulphoxide (Ref 5). It was used in Ger during WWII as a component of a non-fusible expl compn known under the name of Pressling (qv) (Refs 2 4)... 

A rapid and clean oxidation of sulphides to sulphoxides can also be carried out using the titanium(III) trichloride/hydrogen peroxide reagent35. On a milimole scale, the oxidation takes place in a time shorter than 20 min upon addition of a solution of hydrogen peroxide to a solution of the sulphide and titanium(III) trichloride in methanol at room temperature. It was suggested that the formation of a sulphoxide in this reaction resulted from a direct coupling of the hydroxy radical with cation radical 20 formed at the sulphur atom of the sulphide (equation 6). 

A detailed study revealed that sulphides may react with nitric acid to give sulphoxides, sulphones and their nitro derivatives54. However, under suitable conditions the nitric acid oxidation of sulphides leads to a selective formation of sulphoxides. This is probably due to the formation of a sulphonium salt 30 which is resistant to further oxidation50 (equation 12). 

Olah and coworkers56 found that treatment of dialkyl, arylalkyl and diaryl sulphides with nitronium hexafluorophosphate (or tetrafluoroborate) 32 at —78° in methylene chloride resulted in the formation of sulphoxides in moderate to high yields (Table 3). In the oxidation of diphenyl sulphide which affords diphenyl sulphoxide in 95% yield, small amounts of the ring nitration products (o- and p-nitrophenyl phenyl sulphides) were formed. However, diphenyl sulphone and nitrophenyl phenyl sulphoxide were not detected among the reaction products. 

In the reaction between chloramine B and di-(2-chloroethyl)sulphide in aqueous solvents simultaneous formation of di(2-chloroethyl)sulphoxide and the corresponding sulphimide, PhS02N=S(CH2CH2Cl), was observed107. The amount of sulphoxide increased on increasing the concentration of water in the reaction mixture. 

Stereoselective conversion of a thiane 57 to the corresponding tmns-thiane-l-oxide 58 was achieved by bromonium ion mediated electrooxidation while a preferential formation of the cis-sulphoxide 58 was observed under acidic electrolysis123 (equation 38). 

Chromic acid oxidation of sulphides to sulphoxides was reported in 1926124. However, this oxidation procedure is not selective and sulphone formation was observed125. When pyridine was used as a solvent the sulphone formation was strongly reduced126. 

These results may easily be rationalized by assuming that the formation of hydroxy sulphoxides 91, 92 and 93 from hydroperoxysulphides 89 and 90 is an intramolecular oxidation-reduction reaction proceeding through a five-membered transition state 94. However, an alternative intermolecular mechanism in which the approach of the oxidant is directed by the hydroperoxy or the hydroxy function in the reductant cannot be excluded. 

TABLE 8. Formation of sulphoxides, R2S=0, from the reaction of Grignard reagents with sulphurous acid derivatives, SOX2... 

The addition of sulphinyl chlorides to trimethylsilyl enol ether 138 affording a-ketosulphoxides 139 (equation 76) represents an extension of the reaction of sulphinyl chlorides with ketones. This reaction has attracted attention only recently. Sergeev and coworkers192 reported that treatment of sulphinyl chlorides with acyclic enol ethers afforded a-ketosulphoxides 139 in good to excellent yields. Meanwell and Johnson193 observed that in the case of cyclic enol ethers the corresponding sulphoxides were formed only in very low yields. They found, however, that the introduction of an equivalent amount of a Lewis acid into the reaction mixture markedly promotes the desired reaction, whereas the use of catalytic amounts of a Lewis acid led to a substantial reduction in the yield. This is most probably due to the formation of a complex, between the a-ketosulphoxide and the Lewis acid. 

Phenylsulphine prepared in situ from phenylmethanesulphinyl chloride and triethyl-amine reacted with 1 -morpholinocyclohexene to form the addition product 169 having the enamine structure218. A similar experiment with phenylsulphine and 2-pyrrolidinocyclo-hexene gave only 2-phenylmethanesulphinyl cyclohexanone 170. The latter is most probably formed by hydrolysis of the corresponding enamine sulphoxide upon isolation. The reaction of sulphines with enamines is apparently a stepwise process involving the transient formation of the dipolar intermediate 171 which is stabilized by proton transfer, giving the enamine sulphoxide. 

Optically active hydroperoxides 244 were found285 to oxidize prochiral sulphides into the corresponding sulphoxides in higher optical yields (up to 27%) in comparison with those observed with peracids (equation 132). Moreover, the optical purity of the sulphoxides formed may be enhanced by addition of Ti(OPr-i)4. The oxidation of racemic 2-methyl-2,3-dihydrobenzothiophene 246 with these peroxides gave a mixture of cis and trans-sulphoxides 247 (equation 133). In all cases of the oxidation with the hydroperoxide alone the formation of the trans-isomer was strongly preferred and the e.e. value (up to 42%) of the cis-isomer was always higher than that of the trans-isomer. Moreover, the addition of Ti(OPr-i)4 furthermore promoted the selective formation of the frans-sulphoxide 247 and remarkably enhanced the e.e. value of both isomers. 

Formation of optically active sulphoxides was found to occur during oxidation of sulphides in the presence of chiral catalysts. Thus, the oxidation of benzyl methyl sulphide... 

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